Dvace long hot drink
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DVATSE LONG HOT DRINK
Composition:
Active substance: acetylcysteine;
One sachet contains 600 mg of acetylcysteine;
Excipients: sorbitol (E 420), acesulfame potassium, orange flavoring.
Pharmaceutical form. Granules for oral solution.
Main physicochemical characteristics: granules or powder from white to light yellow in color with a characteristic odor. The presence of agglomerates, which easily disintegrate, is possible.
Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents. Acetylcysteine. ATC code R05C B01.
Pharmacological Properties
Pharmacodynamics
N-acetyl-L-cysteine (NAC) exerts a pronounced mucolytic effect on mucous and mucopurulent secretions due to depolymerization of mucoprotein complexes and nucleic acids, which contribute to the viscosity of hyaline and purulent components of sputum and other secretions. Additional properties include reduction of induced mucocyte hyperplasia, increased surfactant production via stimulation of type II pneumocytes, and stimulation of mucociliary apparatus activity, thereby improving mucociliary clearance.
NAC also exerts a direct antioxidant effect through the nucleophilic free thiol (SH) group, which can directly interact with electrophilic groups of reactive oxygen species. Of particular interest is the fact that NAC prevents inactivation of α-1-antitrypsin—an enzyme that inhibits elastase—by hypochlorous acid (HOCl), a potent oxidant produced by myeloperoxidase in activated phagocytes.
Moreover, the molecular structure of NAC allows it to easily penetrate cell membranes. Inside the cell, NAC is deacetylated to form L-cysteine, an essential amino acid for glutathione synthesis. In addition, as a precursor of glutathione, NAC exerts an indirect antioxidant effect. Glutathione is a highly active tripeptide widely distributed in various animal tissues and essential for maintaining cellular functional capacity and morphological integrity. It is, in fact, part of the most important intracellular defense mechanism against both exogenous and endogenous reactive oxygen species and certain cytotoxic substances, including acetaminophen.
Acetaminophen exerts cytotoxic effects by rapidly depleting glutathione levels. NAC plays a crucial role in maintaining adequate glutathione levels, thereby enhancing cellular protection. As a result, NAC serves as a specific antidote in acetaminophen poisoning.
In patients with chronic obstructive pulmonary disease (COPD), administration of 1200 mg of NAC per day over 6 weeks led to a significant increase in inspiratory volume and forced vital capacity (FVC), possibly due to reduced air trapping.
In patients with idiopathic pulmonary fibrosis (IPF), administration of acetylcysteine orally at 600 mg three times daily for one year, in combination with standard IPF therapy (prednisolone and azathioprine), helped preserve vital capacity (VC) and diffusing capacity of the lungs measured by the single-breath carbon monoxide method.
When used as inhalation therapy over one year, NAC contributed to reduced disease progression in patients with IPF.
When administered at very high doses (up to 3000 mg daily for 4 weeks), NAC did not exert significant toxic effects in patients with cystic fibrosis.
The antioxidant efficacy of NAC is associated with a marked reduction in elastase activity in sputum, which is the most significant indicator of lung function in patients with cystic fibrosis. In addition, during treatment, a reduction was observed in the number of neutrophils in the airways, as well as in the number of neutrophils actively releasing elastase-rich granules.
Pharmacokinetics
Absorption
In humans, acetylcysteine is completely absorbed after oral administration. Due to metabolism in the intestinal wall and first-pass effect, the bioavailability of acetylcysteine after oral administration is very low (approximately 10%). No differences have been observed among various dosage forms. In patients with various respiratory and cardiovascular diseases, maximum plasma concentration of acetylcysteine is reached within 1–3 hours after administration and remains high for 24 hours.
Distribution
Acetylcysteine is distributed in the body both in unchanged form (20%) and as metabolites (active) (80%), with predominant detection in the liver, kidneys, lungs, and bronchial secretions. The volume of distribution of acetylcysteine ranges from 0.33 to 0.47 L/kg. Plasma protein binding is approximately 50% four hours after administration and decreases to 20% after 12 hours.
Metabolism and Elimination
After oral administration, acetylcysteine is rapidly and extensively metabolized in the intestinal wall and liver. The metabolite formed, cysteine, is considered active. Subsequently, acetylcysteine and cysteine are metabolized via the same pathway. Approximately 30% of the dose is excreted by the kidneys. The elimination half-life (T1/2) of acetylcysteine is 6.25 hours.
Clinical characteristics.
Indications.
Treatment of acute and chronic diseases of the bronchopulmonary system associated with increased sputum production.
Contraindications.
Known hypersensitivity to acetylcysteine or to any of the excipients of the medicinal product. Active gastric or duodenal ulcer, hemoptysis, pulmonary hemorrhage, severe exacerbation of bronchial asthma.
Interaction with other medicinal products and other forms of interaction.
It is not recommended to dissolve acetylcysteine with other medicinal products in the same glass.
Interaction studies were conducted only in adults.
Concurrent use of acetylcysteine with antitussive agents may increase sputum retention due to suppression of the cough reflex.
Activated charcoal reduces the effectiveness of acetylcysteine.
When administered simultaneously with antibiotics such as tetracyclines (except doxycycline), ampicillin, amphotericin B, cephalosporins, aminoglycosides, interaction with the thiol group of acetylcysteine may occur, leading to reduced activity of both medicinal products. Therefore, the interval between administration of these medicinal products should be at least 2 hours. This does not apply to cefixime and loracarbef.
Significant hypotension and dilation of the temporal artery have been observed when nitroglycerin and acetylcysteine are used concomitantly. In cases where simultaneous use of nitroglycerin and acetylcysteine is necessary, patients should be monitored for hypotension, which may be severe; the possibility of headache should also be considered.
A synergistic effect of acetylcysteine with bronchodilators has been reported.
Acetylcysteine can act as a cysteine donor and increase glutathione levels, promoting detoxification of oxygen free radicals and certain toxic substances in the body.
Acetylcysteine reduces the hepatotoxic effect of paracetamol.
Effect on laboratory tests
Acetylcysteine may interfere with colorimetric assays for salicylates and with the determination of ketone bodies in urine.
Special precautions for use
There have been isolated reports of severe skin reactions (Stevens–Johnson syndrome and Lyell's syndrome) associated with the use of acetylcysteine. Therefore, if any changes in the skin or mucous membranes occur, administration of the drug should be discontinued immediately and a physician should be consulted regarding further treatment.
Acetylcysteine should be prescribed with caution to patients with bronchial asthma due to the possible development of bronchospasm. If bronchospasm occurs, treatment with acetylcysteine must be discontinued immediately.
Caution is recommended when administering the drug to patients with a history of gastric or duodenal ulcer, especially when concomitantly using other medicinal products that irritate the gastric mucosa.
Acetylcysteine should be administered with caution in patients with liver or kidney disease to avoid accumulation of nitrogen-containing compounds in the body.
Acetylcysteine affects histamine metabolism; therefore, prolonged use in patients with histamine intolerance should be avoided, as it may lead to symptoms of intolerance (headache, vasomotor rhinitis, itching).
The use of acetylcysteine, particularly at the beginning of treatment, may cause liquefaction of bronchial secretions and increase their volume. If the patient is unable to effectively expectorate mucus, postural drainage and bronchoaspiration may be required.
Mucolytic agents may cause bronchial obstruction in children under 2 years of age. Due to physiological peculiarities of the respiratory system in this age group, the ability to clear respiratory secretions is limited. Therefore, mucolytics should not be used in children under 2 years of age.
A mild sulfurous odor is not an indication of product deterioration but is characteristic of the active substance.
Important information about excipients
The medicinal product contains sorbitol; therefore, it should not be used in patients with hereditary fructose intolerance.
Use during pregnancy or breastfeeding
Pregnancy
Clinical data on the use of acetylcysteine in pregnant women are limited. Animal studies have not shown any direct or indirect adverse effects on pregnancy, embryofetal development, parturition, or postnatal development.
Breastfeeding period
There is no information available on the passage of acetylcysteine into breast milk.
The medicinal product should be used during pregnancy or breastfeeding only after careful assessment of the benefit–risk ratio.
Ability to influence the reaction rate when driving or operating machinery
There is no evidence that acetylcysteine affects the ability to drive or operate machinery.
Method of Administration and Dosage
Adults and children aged 12 years and older
Administer 600 mg once daily.
The medicinal product should be taken after food.
The contents of the sachet should be dissolved by stirring in ½ glass of cold water, then adding hot, but not boiling, water to make up a full glass. The solution should be drunk after cooling to a comfortable temperature, but no later than 30 minutes after preparation. The sequence of dissolving the powder (cold water first, followed by hot water) must not be changed.
When dissolving acetylcysteine, glassware should be used; contact with metal and rubber surfaces should be avoided.
Additional fluid intake enhances the mucolytic effect of the drug.
The duration of treatment is determined individually by a physician depending on the nature of the disease. In acute uncomplicated conditions, acetylcysteine should be administered for 4–5 days.
Children
For use in children aged 12 years and older.
Overdose.
There are no reported cases of overdose with oral administration of acetylcysteine.
Adult volunteers have taken 11.6 g of acetylcysteine per day for three months without any serious adverse effects.
Acetylcysteine administered at a dose of 500 mg/kg/day does not cause overdose.
Symptoms.
Overdose may manifest with gastrointestinal symptoms such as nausea, vomiting, and diarrhea. In children, there is a risk of hypersecretion.
Treatment.
There is no specific antidote in case of acetylcysteine poisoning; treatment is symptomatic.
Adverse Reactions
Below are the adverse reactions reported after oral administration of acetylcysteine.
All adverse reactions are listed by system organ classes and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).
Ear and labyrinth disorders:
Uncommon – tinnitus.
Respiratory, thoracic and mediastinal disorders:
Rare – dyspnea, bronchospasm (mainly in patients with bronchial hyperreactivity associated with bronchial asthma); frequency not known – rhinorrhea.
Gastrointestinal disorders:
Uncommon – heartburn, stomatitis, abdominal pain, nausea, vomiting, diarrhea; rare – dyspepsia; frequency not known – unpleasant breath odor.
Nervous system disorders:
Uncommon – headache.
Cardiovascular disorders:
Uncommon – tachycardia, decreased blood pressure; very rare – hemorrhages.
Blood and lymphatic system disorders:
Frequency not known – anemia.
Immune system disorders:
Uncommon – hypersensitivity; very rare – anaphylactic shock, anaphylactic/anaphylactoid reactions.
Skin and subcutaneous tissue disorders:
Uncommon – pruritus, urticaria, exanthema, rash, angioneurotic edema (Quincke's edema); frequency not known – eczema.
General disorders:
Uncommon – hyperthermia; frequency not known – facial swelling.
In very rare cases, severe skin reactions (e.g., Stevens−Johnson syndrome and Lyell's syndrome) have been reported in association with acetylcysteine use.
In most cases, at least one other medicinal product may be more likely responsible for the occurrence of mucocutaneous syndrome. If any new skin or mucosal changes occur, acetylcysteine should be discontinued immediately and medical advice should be sought.
Very rarely, bleeding has been reported during acetylcysteine use, which in most cases was associated with hypersensitivity reactions.
Cases of reduced platelet aggregation have been reported; however, there is no clinical confirmation of this effect.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.
Shelf life. 2 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach and sight of children.
Incompatibilities.
Antibiotics and acetylcysteine should not be mixed prior to administration due to the possibility of in vitro inactivation of antibiotics (mainly β-lactam antibiotics).
Packaging.
600 mg/3 g in sachets, 6 sachets per pack.
Availability. Over-the-counter (without prescription).
Manufacturer. JSC "Pharmaceutical company "Darnytsia".
Manufacturer's address.
13 Boryspylska Street, Kyiv, 02093, Ukraine.